Lv Q.-Y.,302 Military Hospital |
Li X.-Y.,Institute for Drug and Instrument Control |
Shen B.-D.,302 Military Hospital |
Dai L.,302 Military Hospital |
And 4 more authors.
Journal of Nanoparticle Research | Year: 2014
The phospholipid-bile salts-mixed micelles (PL-BS-MMs) are potent carriers used for oral absorption of drugs that are poorly soluble in water; however, there are many limitations associated with liquid formulations. In the current study, the feasibility of preparing the fast dissolving oral films (FDOFs) containing PL-BS-MMs was examined. FDOFs incorporated with Cucurbitacin B (Cu B)-loaded PL-sodium deoxycholate (SDC)-MMs have been developed and characterized. To prepare the MMs and to serve as the micellar carrier, a weight ratio of 1:0.8 and total concentration of 54 mg/mL was selected for the PL/SDC based on the size, size distribution, zeta potential, encapsulation efficiency, and morphology. The concentration of Cu B was determined to be 5 mg/mL. Results showed that a narrow size distributed nanomicelles with a mean particle size of 86.21 ± 6.11 nm and a zeta potential of -31.21 ± 1.17 mV was obtained in our optimized Cu B-PL/SDC-MMs formulation. FDOFs were produced by solvent casting method and the formulation with 50 mg/mL of pullulan and 40 mg/mL of PEG 400 were deemed based on the physico-mechanical properties. The FDOFs containing Cu B-PL/SDC-MMs were easily reconstituted in a transparent and clear solution giving back a colloidal system with spherical micelles in the submicron range. In the in vitro dissolution test, the FDOFs containing Cu B-PL/SDC-MMs showed an increased dissolution velocity markedly. The pharmacokinetics study showed that the FDOFs containing PL-SDC-MMs not only kept the absorption properties as same as the PL-SDC-MMs, but also significantly increased the oral bioavailability of Cu B compared to the Cu B suspension (p < 0.05). This study showed that the FDOFs containing Cu B-PL/SDC-MMs could represent a novel platform for the delivery of poorly water-soluble drugs via oral administration. Furthermore, the integration with the FDOFs could also provide a simple and cost-effective manner for the solidification of PL-SDC-MMs. © 2014 Springer Science+Business Media.
Li Y.,PLA Fourth Military Medical University |
Yuan J.,PLA Fourth Military Medical University |
Yang Q.,PLA Fourth Military Medical University |
Cao W.,PLA Fourth Military Medical University |
And 5 more authors.
International Journal of Nanomedicine | Year: 2014
Liposomes constitute one of the most popular nanocarriers for improving the delivery and efficacy of agents in cancer patients. The purpose of this study was to design and evaluate immunoliposome co-delivery of bufalin and anti-CD40 to induce synergetic therapeutic efficacy while eliminating systemic side effects. Bufalin liposomes (BFL) conjugated with anti-CD40 antibody (anti-CD40-BFL) showed enhanced cytotoxicity compared with bufalin alone. In a mouse B16 melanoma model, intravenous injection of anti-CD40-BFL achieved smaller tumor volume than did treatment with BFL (average: 117 mm3 versus 270 mm3, respectively); the enhanced therapeutic efficacy through a caspase-dependent pathway induced apoptosis, which was confirmed using terminal deoxynucleotidyl transferase-mediated dUTP-Fluorescein nick end labeling and Western blot assay. Meanwhile, anti-CD40-BFL elicited unapparent body-weight changes and a significant reduction in serum levels of tumor necrosis factor-a, interleukin-1p, interleukin-6, interferon-y, and hepatic enzyme alanine transaminase, suggesting minimized systemic side effects. This may be attributed to the mechanism by which liposomes are retained within the tumor site for an extended period of time, which is supported by the following biodistri-bution and flow cytometric analyses. Taken together, the results demonstrated a highly promising strategy for liposomal vehicle transport of anti-CD40 plus bufalin that can be used to enhance antitumor effects via synergetic systemic immunity while blocking systemic toxicity. © 2014 Li et al.
Li Y.,PLA Fourth Military Medical University |
Zhao H.,PLA Fourth Military Medical University |
Duan L.-R.,PLA Fourth Military Medical University |
Li H.,PLA Fourth Military Medical University |
And 4 more authors.
Colloids and Surfaces A: Physicochemical and Engineering Aspects | Year: 2014
The aim of this study was to investigate the potential effect of pectin for liposomal drug delivery systems. An orthogonal L9 (33) test was designed to optimize the preparation condition of cationic bufalin liposomes coated with commercially available citrus pectin (CPL). The change in particle size, zeta potential, entrapment efficiency, stability, mucoadhesion and anticancer effect were evaluated. The results showed that CPL had an excellent stability and mucoadhesive properties, and the drug release in vitro was modest prolonged and sustained. Furthermore, the inhibition effect of liposomes on SW480 colon cancer cells was dramatic enhanced due to a block of cell cycle at G0/G1 phase, and CPL had a higher inhibition rate than bufalin liposomes (BFL) because of the anticancer effect of citrus pectin. It is concluded that CPL is a potentially promising drug carrier system treatment for colon cancer. © 2013 Elsevier B.V.
Cheng L.-J.,Hebei North University |
Cheng L.-J.,Institute for Drug and Instrument Control |
Lei H.,Institute for Drug and Instrument Control |
Guo Q.,Institute for Drug and Instrument Control |
Wang Y.-Z.,Institute for Drug and Instrument Control
Academic Journal of Second Military Medical University | Year: 2014
Objective: To explore whether Antrodia cinnamomea can prolong the survival time of stroke-prone spontaneously hypertensive rats, and to investigate the underlying mechanisms from the proteomics perspective. Methods: A total of 80 male stroke-prone spontaneously hypertensive rats were randomly divided into two groups (control group and Antrodia cinnamomea treated group, n= 40). The animals were intragastrically given Antrodia cinnamomea (150 mg/kg). Then the death of the animals in the two groups was observed. Another 6 stroke-prone spontaneously hypertensive rats were randomly divided into drug treatment group and control group, with the drug treatment group intragastrically given Antrodia cinnamomea (150 mg/kg), and the brain proteomics were compared between the two groups 90 days later, with WKY rats used as normal controls. The differentially expressed proteins before and after drug treatment were subjected to mass spectrometry analysis, and the results of mass spectrometry analysis were further confirmed by Western blotting analysis. Results: Antrodia cinnamomea significantly prolonged the survival time of stroke-prone spontaneously hypertensive rats (P < 0.05), and proteomics results showed that Antrodia cinnamomea increased the expression of glutathione S-transferase (GST) and superoxide dismutase (SOD), which were also confirmed by Western blotting analysis. Further study revealed that the total anti-oxidative capability (T-AOC) of the animals was increased (T-AOC; [66.48 ± 16.17] U/g vs [124.75 ± 28.43] U/g, P< 0.05), which was manifested by the increased activity of GST and SOD (GST: [40.33 ± 5.24] U/mg vs [70.50 ± 6.24] U/ mg, P<0.05; SOD; [109.25 ± 23.61] U/mg vs [192.60 ± 23.95] U/mg, P<0.05), and decreased levei of malondialdehyde ([3.96 ± 0.45] nmol/mg vs [2.04 ± 0.31] nmol/mg, P<0.05). Conclusion: Long-term treatment with Antrodia cinnamomea can prolong the lifespan of stroke-prone spontaneously hypertensive rats, which might be related to the increased activity of anti-oxidative enzymes and the decreased oxidative damage.
Kong X.,University of Sichuan |
Kong A.,Institute for Drug and Instrument Control
Current Drug Metabolism | Year: 2014
Tea is an infusion of the leaves of the Camellia sinensis plant and is the most widely consumed beverage in the world after water. The main chemical components in teas are phenolic compounds (tea polyphenols, mainly tea catechins). A large number of in vitro and in vivo scientific studies have supported that the tea polyphenols can provide a number of health benefits such as, reducing the incidence of coronary heart disease, diabetes and cancer. Recently, tea polyphenols have proven highly attractive as lead compounds for drug discovery programs. A clear understanding of chemistry, stability, pharmacokinetics and metabolic fate of tea will be significant to elucidate many medicinal effects by biochemical theory and pharmaceutical development. This article reviews the current literature on the pharmacoknetics and biotransformation of tea catechins. The half-lives of tea polyphenols are 2-4h and their absorption and elimination are rapid in humans. The peak times (tmax) are 1 and 3 h after oral administration and the peak plasma concentrations are low μM range. It has been reported that catechins are easily metabolized by enzyme and microbe, and the main metabolic pathways are methylation, glucuronidation, sulfation, ring-fission metabolism, and so on. The information is important to discuss some of the challenges and benefits of pursuing this family of compounds for drug discovery. © 2014 Bentham Science Publishers.
Kong A.,Institute for Drug and Instrument Control |
Deng A.,Beijing Normal University |
Wu X.,Beijing Normal University |
Qiao J.,Beijing Normal University
Journal of Liquid Chromatography and Related Technologies | Year: 2014
Nuflor (florfenicol) Premix for Swine is approved by the U.S. Food and Drug Administration (FDA) and the same regulatory agencies from many other countries for control of swine respiratory disease. A simple and fast LC-MS/MS method for the assay of florfenicol amine, the marker residue of florfenicol in swine muscle is described. A 24-hr strong acid hydrolysis of tissue residues converts florfenicol and its known metabolites into florfenicol amine and also fully releases florfenicol amine from florfenicol residues covalently bound to the swine muscle. The majority of fatty acids and lipids are removed via hexane extraction. Then, the pH of the extracted hydrolysate is adjusted to 11 and florfenicol amine is extracted by ethyl acetate. A portion of ethyl acetate extract is dried under nitrogen and reconstituted with 1 mL acetonitrile. Dispersive solid-phase extraction is used for cleanup in which 100 mg primary secondary amine sorbent is mixed with the extract. After the centrifugation, the supernatant is diluted 20-fold for a hydrophilic interaction LC-MS/MS analysis. No matrix effect is observed in the LC-MS/MS assay and the recovery is nearly 100%. In the comparison with the current US FDA Center for Veterinary Medicine regulatory surveillance method, the new method is simple, fast, and accurate. The validated method is used to investigate the depletion of florfenicol from the swine administrated with Nuflor (florfenicol) Premix. © 2014 Taylor and Francis Group, LLC.
Han J.,302 Military Hospital of China |
Lv Q.-Y.,302 Military Hospital of China |
Jin S.-Y.,302 Military Hospital of China |
Zhang T.-T.,302 Military Hospital of China |
And 3 more authors.
Chinese Journal of Natural Medicines | Year: 2014
The anti-bacterial activities of three types of di-O-caffeoylquinic acids (diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine (TCM), on Bacillus shigae growth were investigated and compared by microcalorimetry. The three types of diCQAs were 3, 4-di-O-caffeoylquinic acid (3, 4-diCQA), 3, 5-di-O-caffeoylquinic acid (3, 5-diCQA), and 4, 5-di-O-caffeoylquinic acid (4, 5-diCQA). Some qualitative and quantitative information of the effects of the three diCQAs on metabolic power-time curves, growth rate constant k, maximum heat-output power Pm, and the generation time tG, total heat output Qt, and growth inhibitory ratio I of B. shigae were calculated. In accordance with a thermo-kinetic model, the corresponding quantitative relationships of k, Pm, Qt, I and c were established. Also, the half-inhibitory concentrations of the drugs (IC50) were obtained by quantitative analysis. Based on the quantity-activity relationships and the IC50 values, the sequence of inhibitory activity was 3, 5-diCQA > 4, 5-diCQA > 3, 4-diCQA. The results illustrate the possibility that the caffeoyl ester group at C-5 is the principal group that has a higher affinity for the bacterial cell, and that the intramolecular distance of the two caffeoyl ester groups also has an important influence on the anti-bacterial activities of the diCQAs. © 2014 China Pharmaceutical University.
Wang H.-Y.,Shenyang Pharmaceutical University |
Kong A.-Y.,Institute for Drug and Instrument Control |
Yang B.,ZLA Pharmaceutical Technology Co. |
Yan L.-P.,ZLA Pharmaceutical Technology Co. |
Di X.,Shenyang Pharmaceutical University
Yaoxue Xuebao | Year: 2015
A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm × 4.6 mm, 5 μm) with isocratic elution using acetonitrile-20 mmol·L-1 phosphate buffer (pH 3.0, containing 5% methanol) (6:4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg·mL-1 with a lower limit of quantification of 0.5 μg·mL-1, the accuracies were all in standard ranges. The intra- and inter-assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg·kg-1) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The Cmax of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8±4.7, 46.1 ±5.9 and 20.0±2.6 μg·mL-1, respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S-chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1%±36.6% and 76.4%±36.2%, respectively, after intravenous administration of racemic- and R-ibuprofen. This study provides a theoretical basis for the safety of ibuprofen formula of injection drug.
PubMed | PLA Fourth Military Medical University and Institute for Drug and Instrument Control
Type: | Journal: International journal of nanomedicine | Year: 2014
Liposomes constitute one of the most popular nanocarriers for improving the delivery and efficacy of agents in cancer patients. The purpose of this study was to design and evaluate immunoliposome co-delivery of bufalin and anti-CD40 to induce synergetic therapeutic efficacy while eliminating systemic side effects. Bufalin liposomes (BFL) conjugated with anti-CD40 antibody (anti-CD40-BFL) showed enhanced cytotoxicity compared with bufalin alone. In a mouse B16 melanoma model, intravenous injection of anti-CD40-BFL achieved smaller tumor volume than did treatment with BFL (average: 117 mm(3) versus 270 mm(3), respectively); the enhanced therapeutic efficacy through a caspase-dependent pathway induced apoptosis, which was confirmed using terminal deoxynucleotidyl transferase-mediated dUTP-Fluorescein nick end labeling and Western blot assay. Meanwhile, anti-CD40-BFL elicited unapparent body-weight changes and a significant reduction in serum levels of tumor necrosis factor-, interleukin-1, interleukin-6, interferon-, and hepatic enzyme alanine transaminase, suggesting minimized systemic side effects. This may be attributed to the mechanism by which liposomes are retained within the tumor site for an extended period of time, which is supported by the following biodistribution and flow cytometric analyses. Taken together, the results demonstrated a highly promising strategy for liposomal vehicle transport of anti-CD40 plus bufalin that can be used to enhance antitumor effects via synergetic systemic immunity while blocking systemic toxicity.